tamoxifen

Tamoxifen is a selective estrogen receptor modulator (SERM) used primarily in the management of estrogen receptor–positive breast cancer in women and, in some cases, men. It is also used for breast cancer risk reduction in women at high risk. The drug is taken orally, typically as part of adjuvant therapy for several years, though regimens vary.

Tamoxifen acts as an antagonist of the estrogen receptor in breast tissue, blocking estrogen-driven growth of cancer cells. In other tissues it can act as a partial agonist, producing estrogenic effects in bone and the endometrium. This tissue-specific activity explains both its therapeutic benefits and some of its risks, such as effects on bone density and the endometrium.

Tamoxifen is a prodrug that is converted in the liver by enzymes, notably CYP2D6 and CYP3A4, into active metabolites such as endoxifen and 4-hydroxytamoxifen, which have high affinity for the estrogen receptor. Genetic variants in CYP2D6 and interactions with CYP2D6 inhibitors can influence its effectiveness and safety profile.

Common adverse effects include hot flashes and vaginal discharge; long-term use is associated with an increased risk of endometrial changes, including cancer, and with thromboembolic events. Other possible effects include nausea, fatigue, mood changes, and, with prolonged use, occasional ocular effects. Tamoxifen is contraindicated in pregnancy.

In addition to breast cancer treatment and prevention, tamoxifen has been used off-label to induce ovulation in some women with infertility due to anovulation and is occasionally employed in the management of male breast cancer.